Dengue fever (DF) is an acute infectious disease with high incidence in tropical countries, such as Vietnam, where dengue prevention is a challenge for the health sector, government, and policy makers. The aim of this study was to assess the knowledge, attitudes, and practices in southern Vietnam and explore their relationships with the characteristics of the people.A cross-sectional study was conducted, using interviews with 1,906 urban participants and 493 rural participants in southern Vietnam in July 2018.The study found a lack of knowledge regarding DF symptoms, with only 37.2% having a good level of knowledge, although 57.1% had good attitudes and 56.1% had good practices. Television (85.4 %) and the internet (69.5%) were the two main sources of information, and information provided by healthcare professionals was low. Participants with good knowledge had approximately 1.7 times the probability of having a good attitude and 5.0 times the probability of having good practices of those without. Urban participants had 1.3 times the level of knowledge than those in rural areas (p = 0.025), while the quality of attitude scores of rural participants was 1.3 times (p = 0.029) that of urban participants.Improvements in knowledge of DF, as well as in attitudes and practices toward dengue, are required, such as might be achieved through increased publicity and knowledge dissemination.